Vaccines and therapeutics for the encephalitic alphaviruses

This article is a review of vaccines and therapeutics in development for the encephalitic alphaviruses, which includes eastern equine encephalitis virus, western equine encephalitis virus and Venezuelan equine encephalitis virus. The encephalitic alphaviruses are endemic within regions in North and South America. Hosts are normally exposed after being bitten by infectious mosquitoes, and infection can develop into encephalitis in equines and humans with severe rates of morbidity and mortality. These viruses are also potential biological threat agents, being highly infectious via an aerosol route of exposure. In humans, equine encephalitis virus and western equine encephalitis virus are neurotropic viruses targeting the CNS and causing encephalitis. Mortality rates are 50 and 10%, respectively, for these viruses. On the other hand, Venezuelan equine encephalitis virus produces a systemic influenza-like illness with pathogenesis in the lungs and lymphoid tissue in adults and older children. The incidence of encephalitis is less than 5% in younger children with a case-mortality rate of 1%. The host response to virus infectivity is briefly discussed, along with a number of promising therapeutic and prophylactic approaches. These approaches can be broadly classified as: virus-specific, including vaccines, antibody therapy and gene-silencing oligonucleotides; or broad-spectrum, including interferon and activation of the hosts innate immunity.